P-50 Sonodynamic Therapy Synergizes With Chemotherapy to Induce Mitochondrial Apoptosis Via ROS Burst in Hepatocellular and Esophageal Carcinoma.

OBJECTIVES: P-50 is a novel, water-soluble nanomolar porphyrin polymer that has not yet been explored as a sonosensitizer. This study investigates the effects of P-50-mediated sonodynamic therapy (SDT), in combination with oxaliplatin and cisplatin, on hepatocellular carcinoma (HepG2) and esophageal cancer (Eca-109) cells. METHODS: The ultrasonic frequency used was 1.0 MHz, with a power of 1.5 W/cm² and a treatment duration of 30 seconds. The cellular uptake of P-50, the cytotoxic effects and apoptosis in SDT alone, chemotherapy drugs, and their combined application on tumor cells were explored. RESULTS: Results showed efficient uptake of P-50 by both HepG2 and Eca-109 cells. Incubation with 5 μM P-50 for 6 hours exhibited no significant cytotoxicity. Notably, P-50-mediated SDT, when combined with chemotherapy drugs, induced clear signs of late-stage apoptosis and the strongest ROS fluorescence staining in both HepG2 and Eca-109 cells compared to monotherapy. Additionally, an elevated mitochondrial membrane potential was observed in Eca-109 cells, along with the strongest calcium ion fluorescence in HepG2 cells. CONCLUSIONS: These findings suggest that P-50, possessing minimal inherent cytotoxicity, can serve as an effective sonosensitizer for SDT, promoting apoptosis in HepG2 and Eca-109 cells. Furthermore, combined treatment offers a more potent treatment strategy than monotherapy, enhances apoptosis and antitumor effects likely through ROS upregulation, mitochondrial and calcium disorders triggered by SDT.